Polymorphic SERPINA3-R124C reduces pathogenesis of its wild type by shortening the life time of oligomeric Aβ

Author(s):  
Maruf Mohammad Akbor ◽  
Nobuyuki Kurosawa ◽  
Masashi Tanaka ◽  
Masaharu Isobe

Abstract Amyloid beta (Aβ) 42 peptide accumulated in Alzheimer disease (AD) patients’ brain, often colocalized with serine protease inhibitor family A member 3 (SERPINA3). Being a chaperon, SERPINA3 accelerated Aβ42 fibrillization. While analyzing chaperon activity of human SERPINA3 polymorphisms, we found SERPINA3-R124C played a role in protecting cells from Aβ42 cytotoxicity. SH-SY5Y cells exposed to Aβ42 preincubated with wild type SERPINA3 (SERPINA3-WT) resulted in extended toxicity leading cell death whereas Aβ42 with SERPINA3-R124C resulted in less cytotoxicity. Transmission electron microscope and thioflavin T assay revealed that SERPINA3-R124C shortened life time of small soluble oligomer and maintained β-sheet rich protofibril-like aggregates for longer time compared to that of with SERPINA3-WT. Western blot assay confirmed that SERPINA3-R124C converted Aβ42 mostly into high molecular aggregates. Here, we demonstrate first time that polymorphic SERPINA3 acts as a benign chaperon by modulating the transition states of Aβ42, which may contribute to the reduction of AD risk.

Nematology ◽  
2007 ◽  
Vol 9 (3) ◽  
pp. 397-404 ◽  
Author(s):  
Hajime Kosaka ◽  
Manabu Kusunoki ◽  
Vladimir Yushin

AbstractThe dimorphic spermatozoa of the insect-parasitic nematode Deladenus sp. (Tylenchomorpha: Sphaerularioidea: Allantonematidae) were studied for the first time with a transmission electron microscope (TEM). The immature spermatozoa from the testis of mycetophagous males are 10-12 μm diam. and 4-5 μm long unpolarised cells with a centrally located nucleus without a nuclear envelope. The cytoplasm contains mitochondria and specific components, membranous organelles (MO) and fibrous bodies (FB). The MO are spherical vesicles with an internal system of finger-like invaginations of the membrane; the spindle-shaped FB consist of tightly packed parallel fibres. Spermatozoa from the uteri of infective females of Deladenus sp. are vastly different in size being tiny cells ca 2 μm diam. with a spherical or oval nucleus. Each cell contains several mitochondria and MO. Although each individual of Deladenus sp. contains only monomorphic spermatozoa, sperm dimorphism was revealed after analysis of the whole life cycle. Despite a difference in size the cytological characters of both types of spermatozoa conform to the typical rhabditid pattern. The presence of both MO and FB in sphaerularioidid spermatozoa differentiates the superfamily Sphaerularioidea from Tylenchoidea whose representatives lack MO in the spermatogenic cells.


2013 ◽  
Vol 27 (19) ◽  
pp. 1341018 ◽  
Author(s):  
J. M. LIANG ◽  
L. L. HE ◽  
Z. Q. SHEN ◽  
D. L. ZHANG

Europium doped CaAl 2 O 4 nanocones have been grown first time by thermal evaporation method. Scanning electron microscope (SEM) and transmission electron microscope (TEM) were used to analyze the morphology, size and crystal structure of the nanocones. The body of the nanocones are about 2–20 μm in length and their diameters are 200 nm to 1 μm at one end and tapers off to a ~ 40–200 nm at the tip end. The as-synthesized nanocones are single crystalline in monoclinic structure and grow along the [010] direction and the normal direction of (100) and (001). The room temperature photoluminescence (PL) and cathodoluminescence (CL) spectrum measurement reveals that CaAl 2 O 4: Eu 2+ nanocones emit light at about 440 nm.


Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2413 ◽  
Author(s):  
Yubo Liu ◽  
Xinkuan Liu ◽  
Ping Liu ◽  
Xiaohong Chen ◽  
Deng-Guang Yu

To address the life span of materials in the process of daily use, new types of structural nanofibers, fabricated by multifluid electrospinning to encapsulate both epoxy resin and amine curing agent, were embedded into an epoxy matrix to provide it with self-healing ability. The nanofibers, which have a polyacrylonitrile sheath holding two separate cores, had an average diameter of 300 ± 140 nm with a uniform size distribution. The prepared fibers had a linear morphology with a clear three-chamber inner structure, as verified by scanning electron microscope and transmission electron microscope images. The two core sections were composed of epoxy and amine curing agents, respectively, as demonstrated under the synergistic characterization of Fourier transform infrared spectroscopy, thermogravimetric analysis (TGA), and differential scanning calorimetry. The TGA results disclosed that the core-shell nanofibers contained 9.06% triethylenetetramine and 20.71% cured epoxy. In the electrochemical corrosion experiment, self-healing coatings exhibited an effective anti-corrosion effect, unlike the composite without nanofibers. This complex nanostructure was proven to be an effective nanoreactor, which is useful to encapsulate reactive fluids. This engineering process by multiple-fluid electrospinning is the first time to prove that this special multiple-chamber structure has great potential in the field of self-healing.


2016 ◽  
Vol 858 ◽  
pp. 269-273
Author(s):  
Anne Henry ◽  
Hiroshi Yano ◽  
Tomoaki Hatayama

The photoluminescence of the near band gap emission of 10H-SiC is revealed for the first time and detected just below 3.0 eV. The crystallinity thus polytype of the sample is controlled with transmission electron microscope analyses and Laue diffraction. On the photoluminescence spectra up to eight sharp lines are associated to the non-phonon lines of the nitrogen bound exciton even if ten are expected in 10H-SiC. Phonon replicas of these non-phonon lines are observed at lower energy with energy separations similar than those in other hexagonal SiC polytypes. At moderate temperature free-exciton replicas are also observed which allow the determination of the excitonic band gap at 3020.6 meV, value in agreement with the hexagonality of 10H-SiC of 40%. The binding energies associated to the nitrogen bound-excitons are determined as well as the ionization energies of the nitrogen donors in the 10H-SiC polytype.


2011 ◽  
Vol 19 (5) ◽  
pp. 26-29 ◽  
Author(s):  
Xiao Feng Zhang

“Second best no more” was the title of an article written by David C. Joy for Nature Materials. The article was for highlighting a breakthrough made by a team formed between Brookhaven National Laboratory (BNL, USA) and Hitachi High Technologies Corporation (HHT, Japan). Sub-angstrom secondary electron (SE) images were obtained on a Hitachi HD-2700, which is a combined scanning electron microscope (SEM) and scanning transmission electron microscope (STEM) operating at a maximum accelerating voltage of 200 kV. For the first time, single atoms and atomic lattices on crystal surfaces are unambiguously presented in SE images.


Author(s):  
J.A. Chandler ◽  
C.K. Chou

Water-borne copper-chrome-arsenate preservatives(CCA) are now recognised throughout the world as the most effective broad-spectrum preservatives and are extensively used today for a wider range of purposes than any other preservative type. The mode of action of this preservative against decaying fungi, however, is little known and this paper reports investigations into an understanding of the process of treatment. The combination of transmission electron microscopy and x-ray microanalysis has for the first time allowed an accurate location for analysis of the consistuent elements in this preservative when applied to wood.


Proceedings ◽  
2018 ◽  
Vol 2 (13) ◽  
pp. 1001
Author(s):  
Levar Goossen ◽  
Jia Wei ◽  
Gregory Pandraud ◽  
Violeta Prodanovic ◽  
Pasqualina M. Sarro

This paper presents for the first time, the integration of ultra-thin (<10 nm) atomic layer deposition (ALD) aluminum oxide (Al2O3) membranes as electron transparent windows (ETWs) for transmission electron microscope (TEM) nanoreactor applications. The process was successfully implemented and tested in a TEM. ETWs with thicknesses down to 5 and 10 nm were used to image nanoparticles (NPs) in a 120 keV TEM and 200 keV TEM respectively.


2006 ◽  
Vol 519-521 ◽  
pp. 203-208 ◽  
Author(s):  
Tomoyuki Honma ◽  
David W. Saxey ◽  
Simon P. Ringer

The trace addition of Sn (0.01 at.%) to an Al-1.7Cu (at.%) alloy has been investigated using atom probe tomography (APT), transmission electron microscopy (TEM) and high resolution transmission electron microscope (HRTEM). We have studied samples in the as-quenched (AQ) condition and following ageing at both 160 and 200 °C for very short ageing times so as to better understand the early stages of the decomposition processes. Our data reveal independent Cu-Cu and Sn-Sn clusters in the AQ condition, though we did not observe Cu-Sn clustering. We observed for the first time that some of these initial Cu-clusters develop into GP zones during subsequent ageing at temperatures as high as 200 °C. The Sn atom clustering results in precipitation of independent 􀀂- Sn particles after aging for 30 sec. The GP zones consequently undergo reversion and this liberates Cu atoms which seem to participate in a cluster-assisted heterogeneous nucleation of the 􀀃􀀂 phase at the interface of the 􀀂-Sn. For ageing at 200 °C, this process is complete within 180 sec.


2020 ◽  
Vol 21 (6) ◽  
pp. 2228 ◽  
Author(s):  
Raanan Bulvik ◽  
Moshe Biton ◽  
Neville Berkman ◽  
Raphael Breuer ◽  
Shulamit B. Wallach-Dayan

MicroRNAs (miRs) are known to limit gene expression at the post-transcriptional level and have important roles in the pathogenesis of various conditions, including acute lung injury (ALI) and fibrotic diseases such as idiopathic pulmonary fibrosis (IPF). In this study, we found increased levels of miR-34 at times of fibrosis resolution following injury, in myofibroblasts from Bleomycin-treated mouse lungs, which correlates with susceptibility to cell death induced by immune cells. On the contrary, a substantial downregulation of miR-34 was detected at stages of evolution, when fibroblasts resist cell death. Concomitantly, we found an inverse correlation between miR-34 levels with that of the survival molecule FLICE-like inhibitory protein (FLIP) in lung myofibroblasts from humans with IPF and the experimental model. Forced upregulation of miR-34 with miR-34 mimic in human IPF fibrotic-lung myofibroblasts led to decreased cell survival through downregulation of FLIP. Using chimeric miR-34 knock-out (KO)-C57BL/6 mice with miR34KO myofibroblasts but wild-type (WT) hematopoietic cells, we found, in contrast to WT mice, increased and persistent FLIP levels with a more severe fibrosis and with no signs of resolution as detected in pathology and collagen accumulation. Moreover, a mimic of miR-34a decreased FLIP expression and susceptibility to cell death was regained in miR-34KO fibroblasts. Through this study, we show for the first time an inverse correlation between miR-34a and FLIP expression in myofibroblasts, which affects survival, and accumulation in lung fibrosis. Reprogramming fibrotic-lung myofibroblasts to regain susceptibility to cell-death by specifically increasing their miR34a and downregulating FLIP, may be a useful strategy, enabling tissue regeneration following lung injury.


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